Mitotic tethering enables inheritance of shattered micronuclear chromosomes.

ABSTRACT: Chromothripsis, the shattering and imperfect reassembly of one (or a few) chromosome(s)¹, is an ubiquitous² mutational process generating localized and complex chromosomal rearrangements that drive genome evolution in cancer. Chromothripsis can be initiated by mis-segregation errors in mitosis^3,4 or DNA metabolism^5-7 that lead to entrapment of chromosomes within micronuclei and their subsequent fragmentation in the next interphase or following mitotic entry^6,8-10. Here we use inducible degrons to demonstrate that chromothriptically produced pieces of a micronucleated chromosome are tethered together in mitosis by a protein complex consisting of mediator of DNA damage checkpoint 1 (MDC1), DNA topoisomerase II-binding protein 1 (TOPBP1)

SUBMITTER: Trivedi P 

PROVIDER: S-EPMC10424572 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature